Design, Synthesis and Characterization of Novel Coumarin Derivatives
Abstract
Currently, the cholinesterase inhibitors (ChEIs) and an N-methyl-D-aspartate (NMDA) receptor antagonist are the
only approved therapies for Alzheimer's Disease (AD). Coumarins are the phytochemicals with vast biological
activities including AChE inhibition. In this study, several structural change of coumarin derivatives were
introduced by varying the substitution pattern of electron withdrawing (fluorine) and electron donating group
(methoxy) to explore the role of specific positions with respect to biological activity. Among them, compound 2c
shows the highest binding energy value (-10.30 kcal/mol) while 2g show the lowest binding energy (-9.68 kcal/mol)
when being compared to the reference drug, Donepezil (-11.29 kcal/mol) by using molecular docking analysis.
Both compounds were in para position. The starting material was successfully synthesized via Knoevenagel
condensation using piperidium acetate as catalyst with yield of 73.95%. Then, two methods were used for the
second reaction. 60.35% yield of compound 2a was obtained for the first method by carbodiimides coupling to
active carboxylic acid to amide formation in mild reaction condition reaction while the second method gave yield
of 31.02% for compound 2b by using SOCl2 as the activating agent. The targeted compounds were obtained with
impurities. Structural characterization using ATR-FTIR, 1H NMR and 13C NMR were utilized to confirm the
compounds.
Keywords
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